28 results on '"Brossa, Alessia"'
Search Results
2. Aspartate metabolism in endothelial cells activates the mTORC1 pathway to initiate translation during angiogenesis
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Oberkersch, Roxana E., Pontarin, Giovanna, Astone, Matteo, Spizzotin, Marianna, Arslanbaeva, Liaisan, Tosi, Giovanni, Panieri, Emiliano, Ricciardi, Sara, Allega, Maria Francesca, Brossa, Alessia, Grumati, Paolo, Bussolati, Benedetta, Biffo, Stefano, Tardito, Saverio, and Santoro, Massimo M. more...
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- 2022
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3. Urine-derived podocytes from steroid resistant nephrotic syndrome patients as a model for renal-progenitor derived extracellular vesicles effect and drug screening
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Tanzi, Adele, primary, Buono, Lola, additional, Grange, Cristina, additional, Iampietro, Corinne, additional, Brossa, Alessia, additional, Arcolino, Fanny Oliveira, additional, Arigoni, Maddalena, additional, Calogero, Raffaele, additional, Perin, Laura, additional, Deaglio, Silvia, additional, Levtchenko, Elena, additional, Peruzzi, Licia, additional, and Bussolati, Benedetta, additional more...
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- 2024
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4. Profile of matrix‐entrapped extracellular vesicles of microenvironmental and infiltrating cell origin in decellularized colorectal cancer and adjacent mucosa
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Tassinari, Sarah, primary, D'Angelo, Edoardo, additional, Caicci, Federico, additional, Grange, Cristina, additional, Burrello, Jacopo, additional, Fassan, Matteo, additional, Brossa, Alessia, additional, Bao, Riccardo Quoc, additional, Spolverato, Gaya, additional, Agostini, Marco, additional, Collino, Federica, additional, and Bussolati, Benedetta, additional more...
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- 2024
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5. The angiostatic molecule Multimerin 2 is processed by MMP-9 to allow sprouting angiogenesis
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Andreuzzi, Eva, Colladel, Roberta, Pellicani, Rosanna, Tarticchio, Giulia, Cannizzaro, Renato, Spessotto, Paola, Bussolati, Benedetta, Brossa, Alessia, De Paoli, Paolo, Canzonieri, Vincenzo, Iozzo, Renato V., Colombatti, Alfonso, and Mongiat, Maurizio more...
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- 2017
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6. Role of CD133 Molecule in Wnt Response and Renal Repair
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Brossa, Alessia, Papadimitriou, Elli, Collino, Federica, Incarnato, Danny, Oliviero, Salvatore, Camussi, Giovanni, and Bussolati, Benedetta
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- 2018
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7. Goat PRP14 (gPRP14) has xeno-antigenic properties and works as a vaccine in preclinical models of cancer
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Minucci, Saverio, primary, Bussolati, Benedetta, additional, Massa, Paul E., additional, Brossa, Alessia, additional, Ravasio, Roberto, additional, Saadeldin, Mona, additional, Degani, Genny, additional, Papadimitriou, Elli, additional, Saadeldin, Amal, additional, Salvaggio, Antonio, additional, Visintin, Cristina, additional, Rizzi, Giulia, additional, Ricagno, Stefano, additional, Popolo, Laura, additional, Vanoni, Maria Antonietta, additional, and Pelicci, Pier Giuseppe, additional more...
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- 2022
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8. Quinagolide Treatment Reduces Invasive and Angiogenic Properties of Endometrial Mesenchymal Stromal Cells
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Iampietro, Corinne, primary, Brossa, Alessia, additional, Canosa, Stefano, additional, Tritta, Stefania, additional, Croston, Glenn E, additional, Reinheimer, Torsten Michael, additional, Bonelli, Filippo, additional, Carosso, Andrea Roberto, additional, Gennarelli, Gianluca, additional, Cosma, Stefano, additional, Benedetto, Chiara, additional, Revelli, Alberto, additional, and Bussolati, Benedetta, additional more...
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- 2022
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9. Coincubation as miR-Loading Strategy to Improve the Anti-Tumor Effect of Stem Cell-Derived EVs
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Brossa, Alessia, primary, Tapparo, Marta, additional, Fonsato, Valentina, additional, Papadimitriou, Elli, additional, Delena, Michela, additional, Camussi, Giovanni, additional, and Bussolati, Benedetta, additional more...
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- 2021
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10. Extracellular vesicles from human liver stem cells inhibit renal cancer stem cell‐derived tumor growth in vitro and in vivo
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Brossa, Alessia, primary, Fonsato, Valentina, additional, Grange, Cristina, additional, Tritta, Stefania, additional, Tapparo, Marta, additional, Calvetti, Ruggero, additional, Cedrino, Massimo, additional, Fallo, Sofia, additional, Gontero, Paolo, additional, Camussi, Giovanni, additional, and Bussolati, Benedetta, additional more...
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- 2020
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11. Transient Receptor Potential Channel Expression Signatures in Tumor-Derived Endothelial Cells: Functional Roles in Prostate Cancer Angiogenesis
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Bernardini, Michela, Brossa, Alessia, Chinigo, Giorgia, Grolez, Guillaume P., Trimaglio, Giulia, Allart, Laurent, Hulot, Audrey, Marot, Guillemette, Genova, Tullio, Joshi, Aditi, Mattot, Virginie, Fromont, Gaelle, Munaron, Luca, Bussolati, Benedetta, Prevarskaya, Natalia, Pla, Alessandra Fiorio, Gkika, Dimitra, Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Molecular Biotechnology Center, Università degli studi di Torino = University of Turin (UNITO), Service de neurologie et pathologie du mouvement, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), BILILLE, MOdel for Data Analysis and Learning (MODAL), Laboratoire Paul Painlevé (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-École polytechnique universitaire de Lille (Polytech Lille), Dipartimento di Scienze della Vita e Biologia dei Sistemi, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Molecular Biotechnology and Health Sciences, Rôle des canaux ioniques membranaires et du calcium intracellulaire dans la physiopathologie de la prostate, Université de Lille, Sciences et Technologies-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Università degli studi di Torino (UNITO), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Paul Painlevé - UMR 8524 (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-École polytechnique universitaire de Lille (Polytech Lille)-Université de Lille, Sciences et Technologies, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Turin, CHU Lille, CNRS, Inserm, Université de Lille, METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Mécanismes de la Tumorigénèse et Thérapies Ciblées (M3T) - UMR 8161, Physiologie Cellulaire (PHYCEL) - U1003, Physiologie Cellulaire (PHYCELL) - U1003, Santé publique : épidémiologie et qualité des soins - EA 2694, Università degli studi di Torino = University of Turin [UNITO], Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 [PHYCELL], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T], Nutrition, croissance et cancer (U 1069) [N2C], Laboratoire Paul Painlevé - UMR 8524 (LPP), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-École polytechnique universitaire de Lille (Polytech Lille) more...
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[SDV]Life Sciences [q-bio] ,education ,TRP ,calcium channel ,migration ,prostate cancer ,tumor angiogenesis ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Article - Abstract
Background: Transient receptor potential (TRP) channels control multiple processes involved in cancer progression by modulating cell proliferation, survival, invasion and intravasation, as well as, endothelial cell (EC) biology and tumor angiogenesis. Nonetheless, a complete TRP expression signature in tumor vessels, including in prostate cancer (PCa), is still lacking. Methods: In the present study, we profiled by qPCR the expression of all TRP channels in human prostate tumor-derived ECs (TECs) in comparison with TECs from breast and renal tumors. We further functionally characterized the role of the &lsquo, prostate-associated&rsquo, channels in proliferation, sprout formation and elongation, directed motility guiding, as well as in vitro and in vivo morphogenesis and angiogenesis. Results: We identified three &lsquo, genes whose expression is upregulated in prostate TECs: TRPV2 as a positive modulator of TEC proliferation, TRPC3 as an endothelial PCa cell attraction factor and TRPA1 as a critical TEC angiogenic factor in vitro and in vivo. Conclusions: We provide here the full TRP signature of PCa vascularization among which three play a profound effect on EC biology. These results contribute to explain the aggressive phenotype previously observed in PTEC and provide new putative therapeutic targets. more...
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- 2019
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12. Alternative Strategies to Inhibit Tumor Vascularization
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Brossa, Alessia, primary, Buono, Lola, additional, Fallo, Sofia, additional, Fiorio Pla, Alessandra, additional, Munaron, Luca, additional, and Bussolati, Benedetta, additional
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- 2019
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13. Extracellular Vesicles and Carried miRNAs in the Progression of Renal Cell Carcinoma
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Grange, Cristina, primary, Brossa, Alessia, additional, and Bussolati, Benedetta, additional
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- 2019
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14. Anti-tumor activity of stem cell-derived extracellular vesicles
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Brossa, Alessia, primary, Fonsato, Valentina, additional, and Bussolati, Benedetta, additional
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- 2019
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15. Extracellular vesicles from human liver stem cells inhibit tumor angiogenesis
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Lopatina, Tatiana, Grange, Cristina, Fonsato, Valentina, Tapparo, Marta, Brossa, Alessia, Fallo, Sofia, Pitino, Adriana, Herrera-Sanchez, Maria Beatriz, Kholia, Sharad, Camussi, Giovanni, and Bussolati, Benedetta more...
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Cancer Research ,exosomes ,extracellular vesicles ,human liver stem cells ,microRNA ,renal tumor endothelial cells ,tumor angiogenesis ,Oncology ,Neovascularization, Pathologic ,Stem Cells ,Mice, SCID ,Xenograft Model Antitumor Assays ,Extracellular Vesicles ,Mice ,Liver ,Hepatocytes ,Animals ,Humans - Abstract
Human liver stem-like cells (HLSC) and derived extracellular vesicles (EVs) were previously shown to exhibit anti-tumor activity. In our study, we investigated whether HLSC-derived EVs (HLSC-EVs) were able to inhibit tumor angiogenesis in vitro and in vivo, in comparison with EVs derived from mesenchymal stem cells (MSC-EVs). The results obtained indicated that HLSC-EVs, but not MSC-EVs, inhibited the angiogenic properties of tumor-derived endothelial cells (TEC) both in vitro and in vivo in a model of subcutaneous implantation in Matrigel. Treatment of TEC with HLSC-EVs led to the down-regulation of pro-angiogenic genes. Since HLSC-EVs carry a specific set of microRNAs (miRNAs) that could target these genes, we investigated their potential role by transfecting TEC with HLSC-EV specific miRNAs. We observed that four miRNAs, namely miR-15a, miR-181b, miR-320c and miR-874, significantly inhibited the angiogenic properties of TEC in vitro, and decreased the expression of some predicted target genes (ITGB3, FGF1, EPHB4 and PLAU). In parallel, TEC treated with HLSC-EVs significantly enhanced expression of miR-15a, miR-181b, miR-320c and miR-874 associated with the down-regulation of FGF1 and PLAU. In summary, HLSC-EVs possess an anti-tumorigenic effect, based on their ability to inhibit tumor angiogenesis. more...
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- 2018
16. Human liver stem cell-derived extracellular vesicles enhance cancer stem cell sensitivity to tyrosine kinase inhibitors through Akt/mTOR/PTEN combined modulation
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Fonsato, Valentina, primary, De Lena, Michela, additional, Tritta, Stefania, additional, Brossa, Alessia, additional, Calvetti, Ruggero, additional, Tetta, Ciro, additional, Camussi, Giovanni, additional, and Bussolati, Benedetta, additional more...
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- 2018
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17. Effect of the monoclonal antibody TRC105 in combination with Sunitinib on renal tumor derived endothelial cells
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Brossa, Alessia, primary, Buono, Lola, additional, and Bussolati, Benedetta, additional
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- 2018
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18. Differential Sensitivity of Prostate Tumor Derived Endothelial 1 Cells to Sorafenib and 2 Sunitinib
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FIORIO PLA, Alessandra, Brossa, Alessia, Bernardini, Michela, Genova, Tullio, Grolez, G., Villers, A., Leroy, X., Prevarskaya, N., Gkika, D., and Bussolati, Benedetta
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- 2014
19. Extracellular vesicles from human liver stem cells inhibit tumor angiogenesis.
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Lopatina, Tatiana, Grange, Cristina, Fonsato, Valentina, Tapparo, Marta, Brossa, Alessia, Fallo, Sofia, Pitino, Adriana, Herrera‐Sanchez, Maria Beatriz, Kholia, Sharad, Camussi, Giovanni, and Bussolati, Benedetta more...
- Abstract
Human liver stem‐like cells (HLSC) and derived extracellular vesicles (EVs) were previously shown to exhibit anti‐tumor activity. In our study, we investigated whether HLSC‐derived EVs (HLSC‐EVs) were able to inhibit tumor angiogenesis in vitro and in vivo, in comparison with EVs derived from mesenchymal stem cells (MSC‐EVs). The results obtained indicated that HLSC‐EVs, but not MSC‐EVs, inhibited the angiogenic properties of tumor‐derived endothelial cells (TEC) both in vitro and in vivo in a model of subcutaneous implantation in Matrigel. Treatment of TEC with HLSC‐EVs led to the down‐regulation of pro‐angiogenic genes. Since HLSC‐EVs carry a specific set of microRNAs (miRNAs) that could target these genes, we investigated their potential role by transfecting TEC with HLSC‐EV specific miRNAs. We observed that four miRNAs, namely miR‐15a, miR‐181b, miR‐320c and miR‐874, significantly inhibited the angiogenic properties of TEC in vitro, and decreased the expression of some predicted target genes (ITGB3, FGF1, EPHB4 and PLAU). In parallel, TEC treated with HLSC‐EVs significantly enhanced expression of miR‐15a, miR‐181b, miR‐320c and miR‐874 associated with the down‐regulation of FGF1 and PLAU. In summary, HLSC‐EVs possess an anti‐tumorigenic effect, based on their ability to inhibit tumor angiogenesis. What's new? Tumor vascularization is a fundamental step in tumor growth and metastasis. In this study, extracellular vesicles (EVs) released from human liver stem‐like cells (HLSC) inhibited migration of tumor endothelial cells and significantly reduced vessel‐like formation in vitro. Experiments performed in vivo in a SCID mouse model of tumor angiogenesis also showed that HLSC‐EVs were able to inhibit vessel formation and growth. This effect appeared to be specific to HLSC‐EVs, as bone marrow‐derived mesenchymal stem cells EVs displayed no effect. In addition, this anti‐angiogenic feature of HLSC‐EVs was mediated by transfer of specific anti‐angiogenic miRNAs and down‐regulation of predicted target genes. [ABSTRACT FROM AUTHOR] more...
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- 2019
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20. Differential sensitivity of prostate tumor derived endothelial cells to sorafenib and sunitinib
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Fiorio Pla, Alessandra, Brossa, Alessia, Bernardini, Michela, Genova, Tullio, Grolez, Guillaume, Villers, Arnaud, Leroy, Xavier, Prevarskaya, Natalia, Gkika, Dimitra, Bussolati, Benedetta, Rôle des canaux ioniques membranaires et du calcium intracellulaire dans la physiopathologie de la prostate, Université de Lille, Sciences et Technologies-Institut National de la Santé et de la Recherche Médicale (INSERM), Dipartimento di Scienze della Vita e Biologia dei Sistemi, Università degli studi di Torino (UNITO), Molecular Biotechnology Center, Service Urologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, Service d'anatomopathologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), This study was supported by Italian Ministry of University and Research(MIUR) Prin08 to BB and by grants from Ministère de l’Education Nationale,Inserm, France to DG. MB is supported by the Vinci program 2012-UniversitéFranco Italienne., Taibi, Nadia, Università degli studi di Torino = University of Turin (UNITO), Département de neurologie [Lille], Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille more...
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Male ,Niacinamide ,Cancer Research ,Indoles ,Cell Survival ,[SDV]Life Sciences [q-bio] ,Angiogenesis Inhibitors ,Antineoplastic Agents ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,urologic and male genital diseases ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Cell Movement ,Cell Line, Tumor ,Sunitinib ,Genetics ,Humans ,Pyrroles ,Phosphorylation ,Protein Kinase Inhibitors ,Cell Proliferation ,Neoplasm Staging ,Prostate cancer ,Phenylurea Compounds ,VEGF receptor ,Anti-angiogenic therapy ,Endothelial Cells ,Prostatic Neoplasms ,Middle Aged ,Sorafenib ,Vascular Endothelial Growth Factor Receptor-2 ,female genital diseases and pregnancy complications ,Androgen receptor ,Oncology ,Drug Resistance, Neoplasm ,Drug resistance ,Neoplasm Grading ,Biomarkers ,Research Article - Abstract
Background Prostate cancer is the second leading cause of male cancer death in developed countries. Although the role of angiogenesis in its progression is well established, the efficacy of anti-angiogenic therapy is not clearly proved. Whether this could depend on differential responses between tumor and normal endothelial cells has not been tested. Methods We isolated and characterized three lines of endothelial cells from prostate cancer and we tested the effect of Sunitinib and Sorafenib, and the combined treatment with the anti-androgen Casodex, on their angiogenic functions. Results Endothelial cells isolated from prostate tumors showed angiogenic properties and expression of androgen and vascular endothelial cell growth factor receptors. Sunitinib affected their proliferation, survival and motility while Sorafenib only showed a minor effect. At variance, Sunitinib and Sorafenib showed similar cytotoxic and anti-angiogenic effects on normal endothelial cells. Sorafenib and Sunitinib inhibited vascular endothelial cell growth factor receptor2 phosphorylation of prostate cancer endothelial cells, while they differentially modulated Akt phosphorylation as no inhibitory effect of Sorafenib was observed on Akt activation. The combined treatment of Casodex reverted the observed resistance to Sorafenib both on cell viability and on Akt activation, whereas it did not modify the response to Sunitinib. Conclusions Our study demonstrates a resistant behavior of endothelial cells isolated from prostate cancer to Sorafenib, but not Sunitinib. Moreover, it shows the benefit of a multi-target therapy combining anti-angiogenic and anti-hormonal drugs to overcome resistance. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-939) contains supplementary material, which is available to authorized users. more...
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- 2013
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21. Resident Stem Cells and Renal Carcinoma
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Bussolati, Benedetta, Brossa, Alessia, and Camussi, Giovanni
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Article Subject - Abstract
According to the cancer stem cell hypothesis tumors are maintained by a cancer stem cell population which is able to initiate and maintain tumors. Tumor-initiating stem cells display stem or progenitor cell properties such as self-renewal and capacity to re-establish tumors that recapitulate the tumor of origin. In this paper, we discuss data relative to the presence of cancer stem cells in human renal carcinoma and their possible origin from normal resident stem cells. The cancer stem cells identified in human renal carcinomas are not derived from the normal CD133+ progenitors of the kidney, but rather from a more undifferentiated population that retains a mesenchymal phenotype. This population is able to self-renewal, clonogenicity, and in vivo tumor initiation. Moreover, they retain pluripotent differentiation capability, as they can generate not only the epithelial component of the tumor, but also tumor endothelial cells. This suggests that renal cancer stem cells may contribute to the intratumor vasculogenesis. more...
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- 2011
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22. Sunitinib but not VEGF blockade inhibits cancer stem cell endothelial differentiation
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Brossa, Alessia, primary, Grange, Cristina, additional, Mancuso, Letizia, additional, Annaratone, Laura, additional, Satolli, Maria Antonietta, additional, Mazzone, Massimiliano, additional, Camussi, Giovanni, additional, and Bussolati, Benedetta, additional more...
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- 2015
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23. Differential sensitivity of prostate tumor derived endothelial cells to sorafenib and sunitinib
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Fiorio Pla, Alessandra, primary, Brossa, Alessia, additional, Bernardini, Michela, additional, Genova, Tullio, additional, Grolez, Guillaume, additional, Villers, Arnaud, additional, Leroy, Xavier, additional, Prevarskaya, Natalia, additional, Gkika, Dimitra, additional, and Bussolati, Benedetta, additional more...
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- 2014
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24. Presence of osteoinductive factors in bovine colostrum
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Mussano, Federico, primary, Bartorelli Cusani, Alberto, additional, Brossa, Alessia, additional, Carossa, Stefano, additional, Bussolati, Gianni, additional, and Bussolati, Benedetta, additional
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- 2014
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25. Aspartate metabolism in endothelial cells activates the mTORC1 pathway to initiate translation during angiogenesis
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Roxana E. Oberkersch, Giovanna Pontarin, Matteo Astone, Marianna Spizzotin, Liaisan Arslanbaeva, Giovanni Tosi, Emiliano Panieri, Sara Ricciardi, Maria Francesca Allega, Alessia Brossa, Paolo Grumati, Benedetta Bussolati, Stefano Biffo, Saverio Tardito, Massimo M. Santoro, Oberkersch, Roxana E, Pontarin, Giovanna, Astone, Matteo, Spizzotin, Marianna, Arslanbaeva, Liaisan, Tosi, Giovanni, Panieri, Emiliano, Ricciardi, Sara, Allega, Maria Francesca, Brossa, Alessia, Grumati, Paolo, Bussolati, Benedetta, Biffo, Stefano, Tardito, Saverio, and Santoro, Massimo M more...
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Vascular Endothelial Growth Factor A ,Neovascularization, Physiologic ,Mechanistic Target of Rapamycin Complex 1 ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Settore BIO/06 - Anatomia Comparata e Citologia ,angiogenesis ,endothelial metabolism ,Mice ,aspartate metabolism ,Receptors ,Animals ,Humans ,Physiologic ,Molecular Biology ,Neovascularization ,Pathologic ,Aspartic Acid ,Endothelial Cell ,Protein Biosynthesi ,Neovascularization, Pathologic ,mTOR signalling ,Animal ,Vascular Endothelial Growth Factor ,Endothelial Cells ,angiogenesi ,Cell Biology ,tumor angiogenesis ,Vascular Endothelial Growth Factor Receptor-2 ,Pyrimidines ,Receptors, Vascular Endothelial Growth Factor ,Pyrimidine ,Protein Biosynthesis ,Signal Transduction ,tumor angiogenesi ,Developmental Biology ,Human - Abstract
Angiogenesis, the active formation of new blood vessels from pre-existing ones, is a complex and demanding biological process that plays an important role in physiological as well as pathological settings. Recent evidence supports cell metabolism as a critical regulator of angiogenesis. However, whether and how cell metabolism regulates endothelial growth factor receptor levels and nucleotide synthesis remains elusive. We here shown in both human cell lines and mouse models that during developmental and pathological angiogenesis, endothelial cells (ECs) use glutaminolysis-derived glutamate to produce aspartate (Asp) via aspartate aminotransferase (AST/GOT). Asp leads to mTORC1 activation which, in turn, regulates endothelial translation machinery for VEGFR2 and FGFR1 synthesis. Asp-dependent mTORC1 pathway activation also regulates de novo pyrimidine synthesis in angiogenic ECs. These findings identify glutaminolysis-derived Asp as a regulator of mTORC1-dependent endothelial translation and pyrimidine synthesis. Our studies may help overcome anti-VEGF therapy resistance by targeting endothelial growth factor receptor translation. more...
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- 2022
26. The angiostatic molecule Multimerin 2 is processed by MMP-9 to allow sprouting angiogenesis
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Eva Andreuzzi, Rosanna Pellicani, Benedetta Bussolati, Paola Spessotto, Alessia Brossa, Paolo De Paoli, Maurizio Mongiat, Roberta Colladel, Renato Cannizzaro, Alfonso Colombatti, Giulia Tarticchio, Renato V. Iozzo, Vincenzo Canzonieri, Andreuzzi, Eva, Colladel, Roberta, Pellicani, Rosanna, Tarticchio, Giulia, Cannizzaro, Renato, Spessotto, Paola, Bussolati, Benedetta, Brossa, Alessia, De Paoli, Paolo, Canzonieri, Vincenzo, Iozzo, Renato V., Colombatti, Alfonso, and Mongiat, Maurizio more...
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Angiogenesis ,Endothelial cells ,Down-Regulation ,Neovascularization, Physiologic ,Biology ,Matrix metalloproteinase ,Tumor microenvironment ,Molecular Biology ,Cell Line ,Extracellular matrix ,03 medical and health sciences ,Endothelial cell ,Cell Movement ,medicine ,Biomarkers, Tumor ,Human Umbilical Vein Endothelial Cells ,Humans ,Pseudopodia ,Receptor ,Sprouting angiogenesis ,Membrane Glycoproteins ,Neovascularization, Pathologic ,Cell biology ,Endothelial stem cell ,Gene Expression Regulation, Neoplastic ,Angiogenesi ,Vascular endothelial growth factor A ,030104 developmental biology ,Matrix Metalloproteinase 9 ,Antigens, Surface ,Proteolysis ,Matrix Metalloproteinase 2 ,HT29 Cells - Abstract
Angiogenesis is a crucial process occurring under physiological and pathological conditions, including cancer. The development of blood vessels is tightly regulated by a plethora of cytokines, endothelial cell (EC) receptors and extracellular matrix (ECM) components. In this context, we have shown that Multimerin 2 (MMRN2), an ECM molecule specifically secreted by ECs, exerts angiostatic functions by binding VEGFA and other pro-angiogenic cytokines. Here, we demonstrate that during angiogenic stimuli MMRN2 mRNA levels significantly decrease. Furthermore, we provide evidence that MMRN2 is processed by matrix metalloproteinases (MMPs) including MMP-9 and, to a lesser degree, by MMP-2. This proteolytic cleavage correlates with an increased migration of ECs. Accordingly, MMRN2 down-regulation is associated with an increased number of EC pseudopodia at the migrating front and this effect is attenuated using specific MMP-9 inhibitors. The down-modulation of MMRN2 occurs also in the context of tumor-associated angiogenesis. Immunofluorescence performed on tumor sections indicate a broad co-localization of MMP-9 and MMRN2, suggesting that the molecule may be extensively remodeled during tumor angiogenesis. Given the altered expression in tumors and the key role of MMRN2 in blood vessel function, we postulate that analyses of its expression may serve as a marker to predict the efficacy of the treatments. In conclusion, these data further support the role of MMRN2 as a key molecule regulating EC function and sprouting angiogenesis. (C) 2017 Published by Elsevier B.V. more...
- Published
- 2017
27. Urine-derived podocytes from steroid resistant nephrotic syndrome patients as a model for renal-progenitor derived extracellular vesicles effect and drug screening.
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Tanzi A, Buono L, Grange C, Iampietro C, Brossa A, Arcolino FO, Arigoni M, Calogero R, Perin L, Deaglio S, Levtchenko E, Peruzzi L, and Bussolati B
- Abstract
Background: Personalized disease models are crucial for assessing the specific response of diseased cells to drugs, particularly novel biological therapeutics. Extracellular vesicles (EVs), nanosized vesicles released by cells for intercellular communication, have gained therapeutic interest due to their ability to reprogram target cells. We here utilized urinary podocytes obtained from children affected by steroid-resistant nephrotic syndrome with characterized genetic mutations as a model to test the therapeutic potential of EVs derived from kidney progenitor cells., Methods: EVs were isolated from kidney progenitor cells (nKPCs) derived from the urine of a preterm neonate. Three lines of urinary podocytes obtained from nephrotic patients' urine and a line of Alport patient podocytes were characterized and used to assess albumin permeability in response to various drugs or to nKPC-EVs. RNA sequencing was conducted to identify commonly modulated pathways., Results: Podocytes appeared unresponsive to pharmacological treatments, except for a podocyte line demonstrating responsiveness, in alignment with the patient's clinical response at 48 months. At variance, treatment with the nKPC-EVs was able to significantly reduce permeability in all the steroid-resistant patients-derived podocytes as well as in the line of Alport-derived podocytes. RNA sequencing of nKPC-EV-treated podocytes revealed the common upregulation of two genes (small ubiquitin-related modifier 1 (SUMO1) and Sentrin-specific protease 2 (SENP2)) involved in the SUMOylation pathway, a process recently demonstrated to play a role in slit diaphragm stabilization. Gene ontology analysis on podocyte expression profile highlighted cell-to-cell adhesion as the primary upregulated biological activity in treated podocytes., Conclusions: nKPCs emerge as a promising non-invasive source of EVs with potential therapeutic effects on podocyte dysfunction. Furthermore, our findings suggest the possibility of establishing a non-invasive in vitro model for screening regenerative compounds on patient-derived podocytes., Competing Interests: Competing interests The authors have no conflicts of interest to declare. more...
- Published
- 2024
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28. Transient Receptor Potential Channel Expression Signatures in Tumor-Derived Endothelial Cells: Functional Roles in Prostate Cancer Angiogenesis.
- Author
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Bernardini M, Brossa A, Chinigo G, Grolez GP, Trimaglio G, Allart L, Hulot A, Marot G, Genova T, Joshi A, Mattot V, Fromont G, Munaron L, Bussolati B, Prevarskaya N, Fiorio Pla A, and Gkika D
- Abstract
Background : Transient receptor potential (TRP) channels control multiple processes involved in cancer progression by modulating cell proliferation, survival, invasion and intravasation, as well as, endothelial cell (EC) biology and tumor angiogenesis. Nonetheless, a complete TRP expression signature in tumor vessels, including in prostate cancer (PCa), is still lacking. Methods: In the present study, we profiled by qPCR the expression of all TRP channels in human prostate tumor-derived ECs (TECs) in comparison with TECs from breast and renal tumors. We further functionally characterized the role of the ' prostate-associated ' channels in proliferation, sprout formation and elongation, directed motility guiding, as well as in vitro and in vivo morphogenesis and angiogenesis. Results : We identified three ' prostate-associated ' genes whose expression is upregulated in prostate TECs: TRPV2 as a positive modulator of TEC proliferation, TRPC3 as an endothelial PCa cell attraction factor and TRPA1 as a critical TEC angiogenic factor in vitro and in vivo. Conclusions : We provide here the full TRP signature of PCa vascularization among which three play a profound effect on EC biology. These results contribute to explain the aggressive phenotype previously observed in PTEC and provide new putative therapeutic targets. more...
- Published
- 2019
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